Abstract 48: Increasing the racial diversity of lung adenocarcinoma cell lines
Authors: Christopher Leon, Matthew A. Gladstone, Chunli Yan, Diana I. Romero, Yong Huang, Nazarius S. Lamango, Ite A. Offringa
Journal: Cancer Research (2023)

Abstract Lung cancer is a prominent source of cancer health disparities. Black males tend to smoke less, but have a 37% higher chance of developing lung cancer. The three most common histological subtypes of lung cancer are lung adenocarcinoma (LUAD), squamous cell lung cancer (LUSQ), and small cell lung cancer (SCLC). To study lung cancer development, progression, and treatment, numerous tools are needed, including lung cancer cell lines. We undertook a literature and web-based investigation of lung cancer cell line availability from different racial/ethnic groups. We identified 188 cell lines from White individuals, 374 cell lines from Asian subjects, but only 26 cell lines from Blacks and none from Hispanic patients. We conclude that Black and Hispanic lung cancer cell lines are strongly underrepresented. Here we focus on LUAD cell lines since LUAD is the most common histological subtype in all racial/ethnic groups. While 67 White LUAD cell lines have been established, we only identified 5 Black LUAD lines. To remedy this lack of Black LUAD cell lines, we are collecting LUAD samples from Black patients to establish new cell lines (with full consent). In addition, we aim to increase the representation of Black cell lines by creating isogenic cell line variants of existing cell lines, like NCI-H23. NCI-H23 was derived from a Black male patient and carries a KRASG12C heterozygous mutation. We are using CRISPR/CAS9-based genome editing to introduce amino acid substitutions, including KRASG12V and KRASG12A. Our gene editing DNA includes a silent restriction site to help identify edited clones. A fluorescently labeled structured tracrRNA is included during the genomic editing process, allowing the electroporated cells to undergo fluorescence-activated cell sorting. We use the polymerase chain reaction to amplify the relevant genomic region, followed by restriction digestion to identify potential clones and sequencing to confirm successful editing. Several clones are currently under evaluation. Once new hetero- and homozygous KRAS mutants have been identified, we will test the efficacy of polyisoprenylated cysteinyl amide inhibitors (PCAIs). PCAIs have been shown to disrupt the RAS-mediated signaling pathway in racially/ethnically diverse cell lines (manuscript submitted). By generating newly-established and isogenic Black LUAD cell lines, we intend to ensure that potential therapeutics are tested on cell lines with the appropriate racial/ethnic genetic background. In the future, we hope to establish similar cell lines from Hispanic LUAD subjects. Citation Format: Christopher Leon, Matthew A. Gladstone, Chunli Yan, Diana I. Romero, Yong Huang, Nazarius S. Lamango, Ite A. Offringa. Increasing the racial diversity of lung adenocarcinoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 48.